Effective cancer treatment requires complete destruction of cancerous cells while maintaining functionality of the infected organ. Imaging-guided laser surgery provides a good opportunity for conformal delivery of heat generated by diode or other types of lasers to the target. This option permits minimally invasive treatments such as thermal ablation, local hyperthermia sensitization for use in conjunction with radiotherapy, chemo-therapy or brachytherapy, and thermally mediated drug or gene therapy deliveries. Critical to the success of any of these treatments is the ability to provide a reliable prediction of treatment outcome for treatment planning and surgical control at the time of treatment delivery using highly accurate quantitative models. The goal of this project is to develop an MRTI (Magnetic Resonance Temperature Imaging) guided integrative model for prostate cancer using laser surgery and thermotherapy for treatment planning and optimal control of the treatment outcome. Although the proposed study will focus on treatment of prostate cancer, the resulting mathematical framework and computational techniques are quite general. They can be applied to other types of cancers and treatment modalities as well. The specific aims are: [unreadable] 1) To improve and generalize a vasculature-based bio-heat transfer model developed recently, which was based on homogenization theory, for prediction and optimization of laser surgery outcomes in treating prostate cancer; [unreadable] 2) To quantify the reliability of bio-heat transfer models by using models that employ stochastic partial differential equations and conduct sensitivity studies of crucial parameters in the mathematical model; [unreadable] 3) To conduct experiments to characterize the relationship between HSP kinetics and the cause (apoptosis or necrosis) of cell death; and formulate a heat shock protein (HSP) kinetic model in conjunction with a cell damage model that deliver damage measures and HSP expressions as a function of temperature and the duration of time; and finally [unreadable] 4) To integrate bio-heat transfer, HSP and cell damage models into an optimized computer simulation system for treatment planning and laser operation control using MRTI data. [unreadable] [unreadable] The significance of the proposed study is that the integrative system will provide reliable predictions of treatment outcome with quantifiable error estimation. The resulting integrative model will enable design of patient-specific treatment planning based on accurate predictive treatment outcomes. The results produced by this project could dramatically increase the success rates of thermo-therapeutic treatment. [unreadable] [unreadable] [unreadable]